Graft Versus Host Disease Correlates with Increased Survival After Allogeneic Stem Cell Transplant for Mature T-Cell Lymphomas: Evidence of Graft Versus T-Cell Lymphoma Effect.

For aggressive lymphomas a T-cell phenotype confers a poor prognosis. Current therapeutic strategies for T-cell non-Hodgkin lymphoma (NHL) are poorly defined and are associated with a high rate of chemorefractory disease and relapse following chemotherapy +/- autologous stem cell rescue. Allogeneic related and unrelated stem cell transplantation (Allo-HCT) is a potentially curative option, with graft-versus-lymphoma effect as the suggested mechanism for long-term disease control. We report the results of patients with T-cell and NK/T-cell NHL who underwent Allo-HCT at City of Hope National Medical Center.

A consecutive case-series of 38 patients with mature T-cell NHL who underwent Allo-HCT between 2000 and 2007 were included in this analysis. Histologies included: PTCL NOS (n=9); AILD (n=4); ALCL (n=7; four were alk+ and three were alk-); rare histologies (n=6) (NK/T cell nasal and extranasal, enteropathy type, hepatosplenic); and cutaneous T-cell (mycosis fungoides/Sezary syndrome) (n=12). Most patients (n=26, 68%) had advanced disease at the time of transplant. Disease status at transplant: CR1=3, CR2=4, PR after relapse=5, relapse or primary induction failure n=24 and progressive disease at the time of transplant =2. Conditioning regimens consisted of fully ablative regimens (TBI and non-TBI based) in 14 (37%), and reduced intensity (fludarabine/melphalan) in 24 (63%).

The median age at transplant was 43 years (range: 7-74), 74% were male (n=28). The stem cell sources were matched sibling (n=27, 71%) and unrelated donor 39%. The median number of prior regimens was 3 (range: 1-6); 1 patient had a prior autologous transplant. The median follow-up for the 20 (53%) surviving patients is 64 months (range: 16-100). Day 100 mortality was 18%. There were 18 deaths; 5 from disease progression and 13 from transplant-related mortality. A total of 29 patients (78%) developed graft versus host disease (GVHD); six developed only acute GVHD, 10 developed only chronic GVHD and the remaining 13 developed both acute and chronic. The 5-year probabilities of overall (OS) and disease-free (DFS) survival were 51% (95%CI: 42-59%) and 46% (95%CI: 38-53%), respectively. The relapse/progression and non-relapse mortality (NRM) rates at 5 years were 35% (95%CI: 25-48%) and 29% (95%CI: 20-42%) respectively. Analysis for prognostic factors considered predictive for survival showed that the presence or absence of any form of GVHD (either acute grade I-IV or chronic) significantly affected the outcome. The presence of GVHD was significantly associated with improved OS; the estimate OS at 5 years for those with GVHD was 59% (95% CI: 47-69%) versus 25% (95%CI: 18-33%) for those who did not develop acute or chronic GVHD, P=0.007. DFS showed a similar trend, the 5 year survival estimate was 52% (95%CI: 42-62%) for those with GVHD compared to 25% (95%CI: 18-33%) for those without GVHD, P=0.009. As expected the relapse/progression rate among those patients who did not develop acute or chronic GVHD was significantly higher (5 year estimate: 64%, 95%CI: 51-78%) than those who did develop acute and/or chronic GVHD (5 year estimate: 30%, 95%CI: 19-46%), P=0.01.There was no statistically significant difference between OS or DFS for patients who received a fully ablative or reduced intensity conditioning regimen.

In this analysis, the presence of GVHD either acute or chronic was the most important prognostic factor for survival thus strongly supporting a graft-versus-lymphoma effect for T-cell lymphomas. Allo-HCT can confer long-term disease control even in advanced stage patients.

No relevant conflicts of interest to declare.